This research proposal is concerned with the investigation of monoamine metabolism in a population of young adults who have high blood levels of serotonin (hyperserotonemia), among whom the diagnosis of severe idiopathic mental retardation or of infantile autism frequently occurs. The purpose is to identify the cause or nature of the hyperserotonemia that is found with such frequency in this population. We propose to investigate and characterize the physiological or biochemical mechanisms which account for the high blood serotonin levels. We will proceed by measuring the levels of amino acids, monoamines and their metabolites in blood and 24-hour urine samples taken from both these patient groups and also from their parents and siblings (to identify any familial links). Tryptophan loading will be used to enhance the possibility of detecting any abnormal physiological or biochemical mechanism related to the production of high blood serotonin. We also propose to initiate pilot studies in animals (principally rats) to determine whether brain lesions or pharmacological manipulation produced in utero or infancy can cause high blood levels of monoamines, and any of the accompanying biochemical features detected in the human population, severe retardates and autistic disorders. In effect, we will screen animals with central defects for peripheral manifestations of these defects in the hope of discovering an animal model of clinical hyperserotonemia suitable for further investigation. The blood and urinary components to be measured will be separated by solvent extraction column (ion-exchange and gel permeation), gas, and thin-layer chromatogrphy. Quantification will be accomplished by fluorometry, liquid scintillation counting and automatic instrumental scanning of radioactivity, and by the appropriate gas chromatographic detectors.